Introduction: Poor healing of coiled intracranial aneurysms may result in recurrence, a complication that affects one in five patients. Recent studies in animal models have shown cell-therapy with mesenchymal stem cells (MSCs) can improve healing of the aneurysm [1],[2]. However, localized administration of MSCs remains a challenge. A potential solution would be to seed MSCs onto the coils prior to their deployment. Conventional means of promoting attachment of MSCs to surfaces require a culture medium that contains bovine serum. Using bovine serum is undesirable from a clinical point of view, because it is undefined, it varies from batch to batch and it may contain infectious agents. Therefore, finding alternative serum-free means to promote attachment of MSCs to coils is a crucial step in the development of cell-based treatments for intracranial aneurysms. In this study, we have evaluated several defined protein coatings for their ability to promote attachment of MSCs to coils in a serum-free environment.

Methods: Serum-free medium was used to isolate MSCs from mononuclear fraction of bone marrow aspirates obtained from three New Zealand white rabbits. GDC-10 soft detachable coils were coated overnight with collagen I, serum albumin, fibronectin and gelatin. Uncoated coils were used as controls. Each coil was seeded with 50000 MSCs and incubated for 2-3 days. Cell-to-coil attachment was evaluated through light and scanning electron microscopy. A semi-quantitative cell attachment scale of 1-5 was used to quantify microscopy results.

Results: Electron microscopy images for fibronectin and serum albumin coatings scored 1.5-2.5 points higher than collagen and gelatin (Mann-Whitney U, p<0.05) and 0.75-1 point higher than no coating (Kruskal–Wallis, p=0.24). Light microscopy attachment scores were on average 0.56 points higher in all coatings compared with no coating (Kruskal–Wallis, p=0.20).

Conclusions: Cell attachment substrate proteins enable seeding of MSCs onto the coils in a clinically translatable serum-free culture medium.

Patient Care: This work contributes to current efforts towards preventing aneurysm recurrence after endovascular coiling, a complication that affects one in every five patients.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe incidence and clinical implications of aneurysm recurrence after endovascular coiling 2) Discuss, in small groups, the potential of cell therapy in preventing recurrence 3) Identify an effective way to attach mesenchymal stromal cells to detachable coils in the absence of serum.

References: [1] A. Rouchaud, C. Journé, L. Louedec, V. Ollivier, M. Derkaoui, J.-B. Michel, and M. Mazighi, “Autologous mesenchymal stem cell endografting in experimental cerebrovascular aneurysms.,” Neuroradiology, vol. 55, no. 6, pp. 741–9, Jun. 2013. [2] A. Kuwabara, J. Liu, J.-W. Lee, and T. Hashimoto, “Human Mesenchymal Stem Cells Reduce the Rupture Rate of Intracranial Aneurysm,” Anesthesiology 2014 Meeting, 2014.